title: Structural transitions associated with the interaction of Alzheimer beta-amyloid peptides with gangliosides.
abstract: Alzheimer's disease is characterized pathologically by the presence of neurofibrillary tangles and amyloid plaques. The principal component of the plaque is the beta-amyloid peptide (Abeta), a 39-43-residue peptide. The conformational change required for the conversion of soluble peptide into amyloid fibrils is modulated by pH, Abeta concentration, addition of kinetic and thermodynamic enhancers, and alterations in the primary sequence of Abeta. We report here the ability of gangliosides to induce an alpha-helical structure in Abeta and thereby diminish fibrillogenesis. Circular dichroism and a fluorescence dye release assay data indicate that gangliosides interact with and induce alpha-helix formation in Abeta. We find that the sialic acid moiety of gangliosides is necessary for the induction of alpha-helical structure. Differences in the amount and the position of the sialic acid on the carbohydrate backbone also affect the conformational switch. The Abeta-ganglioside interaction at pH 7.0, monitored by CD, is stable over time and resistant to high concentrations of NaCl. The induction of alpha-helical structure is greater with Abeta1-40 than Abeta1-42. The ability of gangliosides to sequester Abeta from fibril formation was also evaluated by electron microscopy.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, Canada.
authors.forename: J
authors.initials: J
authors.lastname: McLaurin
authors.forename: T
authors.initials: T
authors.lastname: Franklin
authors.forename: P E
authors.initials: PE
authors.lastname: Fraser
authors.forename: A
authors.initials: A
authors.lastname: Chakrabartty
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D008854:Microscopy, Electron; D009994:Osmolar Concentration; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D016229:Amyloid beta-Peptides; D005732:Gangliosides